Abstract

BACKGROUND. Loss of heterozygosity (LOH) at chromosome 10q25-q26 has been
reported previously in endometrial carcinoma (EC), suggesting the presence of
tumor suppressor gene(s). Nevertheless, frequency of genome-wide microsatellite
instability (MSI) has been demonstrated higher in EC than in other common
malignancy, mostly due to defective DNA mismatch repair. The authors further
evaluated the role of the chromosome 10q25-q26 in endometrial tumorigenesis as
well as the clinical significance of any observed genetic alteration in sporadic EC.
METHODS. Paired normal and tumor samples from 94 Sardinian patients with
sporadic EC at various stages of disease were screened by polymerase chain
reaction (PCR)–based microsatellite analysis. Genomic DNA was isolated from
paraffin embedded tissues and amplified by PCR using microsatellite markers
spanning approximately 14 cM at 10q25-q26. Microsatellite instability was studied
at four loci mapping to different chromosomal locations.
RESULTS. Thirty-two (34%) EC patients were found negative for genetic alterations
within the 10q25-q26 region. Among the remaining 62 (66%) EC cases, the authors
identified 1) a minimum consensus region of LOH of approximately 1 cM, between
D10S610 and D10S542 markers; and 2) a subset of tumors with prevalence of
instability at 10q25-q26 (10qMI +), as expression of the presence of a MSI + phenotype.
CONCLUSIONS. The authors’ data establish the existence of significant correlations
between disease stages and 10qMI + (with or without MSI +). However, longer
follow-up and additional studies are required to define the clinical significance of
these findings as prognostic factors. Moreover, the minimum region of LOH at
10q25-q26 will be further analyzed for identifying the putative tumor suppressor
gene involved in EC pathogenesis.